Chance WT, Dayal R, Friend L, Sheriff S (2004) Intraventricular injection of CRF receptor 2 antisense oligonucleotide reduces burn-induced hypermetabolism. Neuroscience 2004 Abstracts 890.22. Society for Neuroscience, San Diego, CA.
Summary: Following major burn trauma, mammals exhibit a prolonged hypermetabolic response proportional to the size of the burn. The ability to control metabolic rate would likely result in better clinical management of burn patients. Our research employing a saporin-CRF conjugate to lesion CRF receptors suggested that activity at CRF receptor(R)-2 mediated increased resting energy expenditure (REE) in burned rats. In the present study we assessed whether treatment of burned rats with antisense oligonucleotides (ON) to CRF or CRF R-2 would reduce REE. Following anesthetization (ketamine/xylazine:80/15 mg/kg,), cannulae (24 ga) were implanted into the 3rd ventricle of 52 adult, male, SD rats. Two weeks later, these rats were anesthetized and subjected to a 25 sec, 30% body surface area, open flame burn (n = 30) or sham burn procedures (n = 22). Following (2-6 days) the burn trauma, either sense or antisense ONs to CRF (15 ug) or CRF R-2 (20 ug) was injected, ivt. REE (kcal/kg/24 hrs) was determined in these rats 7 and 14 days after burn by indirect calorimetry. Treatment with CRF antisense ON did not reduce REE in any groups. Burned rats given the CRF R-2 sense ON exhibited significant hypermetabolism both 7 (188±5 vs 156± 9) and 14 (201±8 vs 151±14) days post-burn, as compared to sham-burned rats. Burned rats treated with the CRF R-2 antisense ON were not significantly different from sham burned rats 7 (169±8) or 14 (167±5) days post-burn. Since the antisense treatment should decrease translation of message into protein at the receptor, these results suggest that activity at the CRF-2 receptor is necessary for expression of burn-induced hypermetabolism. Therefore, it is possible that CRF-2 receptor antagonists could be useful in treating burn-induced hypermetabolism.
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